Membrane presynaptic

The influx of Ca(Il) across the presynaptic membrane is essential for nerve signal transmission involving excitation by acetylcholine (26). Calcium is important in transducing regulatory signals across many membranes and is an important secondary messenger hormone. The increase in intracellular Ca(Il) levels can result from either active transport of Ca(Il) across the membrane via an import channel or by release of Ca(Il) from reticulum stores within the cell. More than 30 different proteins have been linked to regulation by the calcium complex with calmoduhn (27,28). 

Neurotransmitter Transporters. Figure 3 Dopamine turnover at a presynaptic nerve terminal, (a) Dopamine is produced by tyrosine hydroxylase (TH). When secretory vesicles are filled, they join the releasable pool of vesicles at the presynaptic membrane. Upon exocytosis, the diffusion of released dopamine is limited by reuptake via DAT. (b) If DAT is inactive, dopamine spreads in the cerebrospinal fluid but cannot accumulate in secretory vesicles. This results in a compensatory increase of dopamine hydroxylase activity and a higher extracellular dopamine level mice with inactive DAT are hyperactive. 

Acetylcholine, which is set free from vesicles present in the neighbourhood of the presynaptic membrane, is transferred into the recipient cell through this channel (Fig. 6.25). Once transferred it stimulates generation of a spike at the membrane of the recipient cell. The action of acetylcholine is inhibited by the enzyme, acetylcholinesterase, which splits acetylcholine to choline and acetic acid. 

G -protein-coupled receptors are often located on the presynaptic plasma membrane where they inhibit neurotransmitter release by reducing the opening of Ca2+ channels like inactivation and breakdown of the neurotransmitter by enzymes, this contributes to the neuron s ability to produce a sharply timed signal. An a2 receptor located on the presynaptic membrane of a noradrenaline-containing neuron is called an autoreceptor but, if located on any other type of presynaptic neuronal membrane (e.g., a 5-HT neuron), then it is referred to as a heteroreceptor (Langer, 1997). Autoreceptors are also located on the soma (cell body) and dendrites of the neuron for example, somatodendritic 5-HTia receptors reduce the electrical activity of 5-HT neurons. 

FIGURE 43-2 Photomicrograph of the human neuromuscular junction. In normal muscle, Ach receptors are associated with the terminal expansions of the junctional folds and the architecture of the postjunctional membrane follows closely the distribution of active zones in the presynaptic membrane, b, basal lamina I, infoldings m, mitochondria M, myocyte N, nerve terminal r, ribosomes s, synaptic space S, Schwann cell. Courtesy of A. Engel. 

Another example of molecular communication is found in a neuronal synapse, which is a communication junction between two neurons as shown in Fig.2. The presynaptic membrane releases the neurotransmitter molecule that is recognized and captured by the receptor located on the surface of the postsynaptic membrane. 

Figure 21.1 A schematic drawing of a synapse. The synaptic terminal is shown activated. Synaptic vesicles are fusing with the presynaptic membrane and releasing a neurotransmitter that diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane. This triggers a new nerve impulse. (Redrawn from D. Voet and J. G. Voet, Biochemistry, 3rd edn, 2004. Donald and Judith G. Voet. Reprinted with permission of John Wiley and Sons, Inc.)...

Figure 14.11 Effects of excitatory and inhibitory neurotransmitters on initiation of an action potential in response to a second neurotransmitter. If the neurotransmitter released from the presynaptic membrane is inhibitory, it will reduce the likelihood that the second neurotransmitter will initiate an action potential. If the neurotransmitter is excitatory, it will increase the likelihood that the second neurotransmitter will initiate an action potential in the postsynaptic neurone. The second neurotransmitter arises from synapses of other axons.

Vesicles move towards the presynaptic membrane and fuse with it. 

The inhibitory effect of a2 agonists on noradrenaline release involves a hyperpolarization of the presynaptic membranes by opening potassium ion channels. The reduction in the release of noradrenaline following the administration of an a2 agonist is ultimately due to a reduction in the concentration of free cytosolic calcium, which is an essential component of the mechanism whereby the synaptic vesicles containing noradrenaline fuse to the s)maptic membrane before their release. 

The a.1 receptors are excitatory in their action, while the a2 receptors are inhibitory, these activities being related to the different types of second messengers or ion channels to which they are linked. Thus, a2 receptors hyperpolarize presynaptic membranes by opening potassium ion channels, and thereby reduce noradrenaline release. Conversely, stimulation of ai receptors increases intracellular calcium via the phosphatidyl inositol cycle which causes the release of calcium from its intracellular stores protein kinase C activity is increased as a result of the free calcium, which then brings about further changes in the membrane activity. 

Interaction of OA with a specific receptor located on the surface of the responding cell or on the presynaptic membrane of the releasing cell. 

The decisive element in exocytosis is the interaction between proteins known as SNAREs that are located on the vesicular membrane (v-SNAREs) and on the plasma membrane (t-SNAREs). In the resting state (1), the v-SNARE synaptobrevin is blocked by the vesicular protein synaptotagmin. When an action potential reaches the presynaptic membrane, voltage-gated Ca "" channels open (see p. 348). Ca "" flows in and triggers the machinery by conformational changes in proteins. Contact takes place between synaptobrevin and the t-SNARE synaptotaxin (2). Additional proteins known as SNAPs bind to the SNARE complex and allow fusion between the vesicle and the plasma membrane (3). The process is supported by the hydrolysis of GTP by the auxiliary protein Rab. 

All chemical synapses function according to a similar principle. In the area of the synapse, the surface of the signaling cell presynaptic membrane) is separated from the surface of the receiving cell (postsynaptic membrane)... 

H3-receptors have been identified in the central nervous system. They are located on presynaptic membranes and serve as inhibitory autoreceptors at histaminergic neurons. They are also found on certain human autonomic nerve endings and in atrial tissue where they may inhibit norepinephrine release during ischemia. 

Neuromuscular transmission involves the events leading from the liberation of acetylcholine (ACh) at the motor nerve terminal to the generation of end plate currents (EPCs) at the postjunctional site. Release of ACh is initiated by membrane depolarization and influx of Ca++ at the nerve terminal (Fig. 28.1). This leads to a complex process involving docking and fusion of synaptic vesicles with active sites at the presynaptic membrane. Because ACh is released by exocytosis, functional transmitter release takes place in a quantal fashion. Each quantum corresponds to the contents of one synaptic vesicle (about 10,000 ACh molecules), and about 200 quanta are released with each nerve action potential. 

Mechanism of Action A tricyclic antidepressant that blocks the reuptake of neu-retransmitters, including norepinephrine and serotonin, at presynaptic membranes, thus increasing their availability at postsynaptic receptor sites. Also has strong anticholinergic activity. Therapeutic Effect Relieves depression. 

Mechanism of Action An antidepressant that appears to inhibit serotonin and norepinephrine reuptake at CNS neuronal presynaptic membranes is a less potent inhibitor of dopamine reuptake. Therapeutic Effect Relieves depression. Pharmacokinetics Well absorbed from the G1 tract. Protein binding greater than 90%. Extensively metabolized to active metabolites. Excreted primarily in urine and, to a lesser extent, in feces. Half-life 8-17 hr. 

Mectianism of Action An antidepressant, anxiolytic, and antiobsessional agent that selectively blocks uptake of the neurotransmitter serotonin at neuronal presynaptic membranes, thereby increasing its availability at postsynaptic receptor sites. Therapeutic Effect Relieves depression, reduces obsessive-compulsive behavior, decreases anxiety. 

Mechanism of Action A tricyclic antidepressant that increases synaptic concentration of norepinephrine and/or serotonin by inhibiting their reuptake by presynaptic membranes. Therapeutic Effect Produces antidepressant effect. 

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